The Cystic Fibrosis Research Center at the University of Pittsburgh currently has 55 members in eight departments and garners nearly $10 M in external grants and contracts to support its CF research efforts. These are focused in three major areas: The Center has a strong basic science component that addresses the Cell and Molecular Biology of CF, and is supported by NIH, NSF and Cystic Fibrosis Foundation (CFF) grants. Investigators in this group make extensive use of differentiated, primary human bronchial epithelia (HBE) for their work. They employ the methods of biochemistry, molecular biology, cell biology and electrophysiology to study CFTR and ENaC functions in epithelial membranes, how these pathways contribute to normal airway function, how they are trafficked between various compartments of the protein secretory and recycling pathways, and how pharmacological manipulation of channel biogenesis (correction) or channel activity (potentiation) influence HBE function. Studies of Lung Infection and Inflammation focus on the pulmonary inflammatory response to bacterial infection in HBE and animal models. These studies aim to improve our understanding of CF disease pathogenesis, define bio-markers for clinical trials, and identify targets for anti-inflammatory therapy. The Clinical Studies group translates basic findings into new therapies. It develops and evaluates methods to improve airway drug delivery and isotopic clearance assays that assess transmural airway liquid movements in vivo, to test therapeutics that target the core defect in CF. The proposed Research and Translational Core Center will be directed by Dr. Raymond Frizzell while Dr. Joseph Pilewski will serve as Associate Director. The Center is comprised of three scientific cores: Human Airway Cell and Assays (Frizzell, PI), Clinical Studies/Outcomes (Pilewski, PI), and Imaging (Watkins, PI). The Core Center will operate a Pilot and Feasibility Program to bring new investigators into CF research. This Center emphasizes the translation of basic knowledge into applied therapeutics.